S. Andreoli, Scott Revkees, M. Bull
Oct 1, 1995
Dr. Proesmans had an excellent idea when he suggested that Pediatric NephroIogy add a section to the journal to discuss diagnostic problems and unusual cases. The first "A Case for Diagnosis" reported a child with Down syndrome, hypercalcemia, hypercalciuria, and medullary nephrocalcinosis with renal insufficiency . Interestingly, we have seen a nearly identical case. Our patient was born at term with a birth weight of 2.93 kg after a pregnancy complicated by maternal preeclampsia. She had the typical features of Down syndrome which was confirmed by karyotyping. At 14 months of age, an echocardiogram demonstrated a moderate atrial septal defect (ASD) secundum, but she did not have a cardiac murmur or clinical symptoms of heart disease. At 18 months of age she was hospitalized for failure to thrive with a weight of 6.5 kg, length of 70 cm, and occipital frontal circumference (OFC) 42.3 cm (each less than the 5% for children with Down syndrome) . The social history was chaotic; the parents were recently divorced and the patient and her mother were living in a cooperative living environment. Her diet consisted of 20 calorie/oz infant formula and occasional servings of table foods. A precise dietary history could not be obtained from the mother. Physical examination demonstrated features typical of Down syndrome. The blood pressure was 102/60 mmHg. Initially laboratory studies demonstrated that the total serum calcium was 14.4 mg/dl (normal 8.4-10.6 mg/dl), phosphorus 5.5 mg/dl, sodium 135 mEq/1, potassium 4.5 mEq/1, chloride 99 mEq/1, bicarbonate 19 mEq/1, creatinine 1.0 mg/dl, and the blood urea nitrogen 31 mg/dl. With hydration her total serum calcium declined to 12.2 mg/ dl (ionized calcium was 6.6 mg/dl, normal 4 .5-5.3 mg/dl); urinalysis revealed 5 1 0 white blood cells per high-power field and a urine culture no growth; a urine calcium/creatinine ratio was markedly elevated at 1.11 and a renal ultrasound examination demonstrated bilateral diffuse medullary hyperechogenicity consistent with nephrocalcinosis. In addition, there was cortical thinning and each kidney was smaller than two standard deviations below the mean. Her serum thyroxine was 9.2 gg/dl (normal 5 1 2 gg/ dl), triiodothyronine (T3) 178 ng/dl (normal 75 -220 ng/dl) and the thyroid-stimulating hormone (TSH) was 8.8 gIU/mi (normal 0 .2-6.2 gIU/ml). A mildly elevated TSH was confirmed and she began therapy with 37.5 gg Synthroid levothyroxine sodium (Boots Pharmaceuticals Lincolnshire, Illinois) each day. The intact parathyroid hormone was suppressed at 6.5 pg/ml (normal 10-65 pg/ml), the 25dihydroxyvitamin D level was 33 ng/ml (normal 9 5 2 ng/ ml), and the 1,25-dihydroxyvitamin D level was 6 pg/ml (normal 15-60 pg/ml). A bone scan was normal and there was no evidence of malignancy. She was initially treated with hydration and calcium restriction. After discharge from the hospital, she continued to demonstrate failure to thrive, mild hypercalcemia, and hypercalciuria, although urine calcium/creatinine ratios were reduced to 0.56 and 0.375 compared with ratios at the time of admission. When all laboratory studies were completed, approximately 1 month after her initial presentation with severe hypercalcemia, she was begun on a low-calcium formula as her laboratory studies did not demonstrate a primary cause for hypercalcemia. Since the initiation of the low-calcium formula, her serum calcium level has been approximately 10.7 mg/dl and the serum creatinine has declined to 0.5 mg/dl, while the urine calcium/creatinine ratio is 0.32. Six months after the initial presentation with severe hypercalcemia a renal ultrasound examination was unchanged. In summary, our patient with Down syndrome presented with severe hypercalcemia, hypercalciuria, elevated serum creatinine, and medullary nephrocalcinosis. Similar to the previously reported case, our patient did not have hyperparathyroidism, vitamin D intoxication, malignancy, or other identifiable causes of hypercalcemia. Our patient had a very mildly elevated TSH with normal T3 and T4 levels, demonstrating that she was euthyroid. In each of the children, dietary calcium restriction resulted in reduced serum calcium levels, decreased urine calcium/creatinine ratios, and a decline in serum creatinine levels. The similarity of the clinical and laboratory findings in these two children with Down syndrome suggest a possible genetic predisposition to excess absorption of dietary calcium. Perhaps hormones, receptors, or other factors important in the regulation of calcium absorption are localized to chromosome 21, and overexpression could lead to excess absorption of calcium in appropriate dietary circumstances. We are interested to know if other physicians caring for children with Down syndrome have seen similar cases.